The ten-year (1993-2002) Baltimore Longitudinal Study of Aging prostate aging and disease study has both retrospective and prospective arms involving repeated assessments of anatomical, physiological, hormonal, and behavioral aspects of age-associated changes in prostate size. A major goal of the study is to identify antecedents of prostate cancer and benign prostatic hyperplasia (BPH). Current research is addressing the question of when serial measures of PSA are necessary. Over the past year, we have demonstrated that normal levels of PSA can be used as a risk factor for the development of prostate cancer as long as 30 years prior to diagnosis in 40-50 year old men, and 15-20 years earlier in 50-60 year old men. The findings argue the potential to identify men at increased risk. We are now trying to identify the best strategy for the use of PSA in these men at increased risk. To do this, we are examining the impact of PSA velocity on cancer diagnosis in men with PSA values between 2 an 4 ng/ml, a level that currently is felt to be associated with increased cancer risk, particularly in men less than 60 years of age. We have examined other factors that may be associated with increased prostate cancer risk. Men who have a large prostate gland are at increased risk for the subsequent diagnosis of prostate cancer. What is unclear is whether the cancer is directly related to gland size, or if it is an artifact of both cancer and benign growth leading to elevated PSA levels. We have analyzed the impact of stratifying normal PSA levels in younger men on the size of their glands years later. When 40 year old men are stratified by quartile of PSA, those men with a PSA above approximately 0.6 are at increased risk of having a large gland over the subsequent 25 years. We have also examined whether serum selenium levels correlated with the risk of later development of prostate cancer using a case control design. Cases included 52 men who were compared to 96 age matched controls with no detectable prostatic disease. Serum selenium levels were found to decrease with increasing age. The risk of prostate cancer was lower in men with serum selenium levels above the lowest quartile with odds ratios of .29,.34, and .48 for subsequent quartiles (p=0.049). Age of the patients at diagnosis did not affect the protective effect observed for higher selenium values. The findings are consistent with other reports that higher serum selenium levels may be associated with a decreased risk of prostate cancer. At this point, we cannot address whether supplemental selenium may reduce the risk of prostate cancer. We have examined whether Insulin like growth factors (IGF) play a role in prostate growth, hyperplasia and malignancy. High serum levels of IGF-I and low levels of IGF-II were found to be independently associated with increased risk of prostate cancer. However, PSA level is a much stronger predictor of the prostate cancer in the ensuing 10 years than either IGF-I or IGF-II. In addition, an absence of a relationship was found between IGF-I and prostate size suggesting that the increased risk of prostate cancer associated with higher IGF-I levels is not due to increased ascertainment in men with large prostates.